At the molecular level dopaminergic function is regulated by several important proteins including dopamine transporters (DAT), vesicular monoamine transporters (VMAT), tyrosine hydroxylase (TH) and possibly alpha synuclein. Dopaminergic areas in the brain are extremely vulnerable to the effects of oxidative stress, and heavily affected during senescence. Any disruption to dopaminergic homeostasis could lead to an increase to the age related declines in dopaminergic functions. The currrent literature suggest that chronic psychostimulant abuse results in alterations to dopaminergic function via changes in the important dopaminergic proteins metioned above. The overall goal of this project is to examine the longterm effects of continuous chronic cocaine and methamphetamine administration on the long term expression of DAT, VMAT, TH, and alpha synuclein, and to determine the age related consequenes on dopaminergic function. In addition, we will asses how these changes affect age related declines in psychomotor and cognitive function. To meet these goals, we have the following specific aims:1.) Determine if chronic psychostimulant adminstration has any long term consequences on the expression of alpha synuclein, DATA/MAT, and TH or levels of oxidative stress in various regions of the brain. 2.) Determine if a relationship exists between continuous chronic cocaine and methamphetamine administration and increases in age-related impairments in cognitive and psychomotor functions.To meet these aims, we will employ both behavioral and biochemical techniques. As a whole, these studies will aid in our understanding of the long term effects of psychostimulant abuse and the neurochemistry which underlie these processes. [unreadable] [unreadable] [unreadable]